Peripheral GLP-1 gastroprotection against ethanol: the role of exendin, NO, CGRP, prostaglandins and blood flow.
The aim of this study was to investigate the effects of peripherally injected glucagon like peptide-1 (GLP-1) on ethanol-induced gastric mucosal damage and the mechanisms included in the effect. Absolute ethanol was administered through an orogastric cannula right after the injection of GLP-1 (1, 10, 100, 1000 or 10,000 ng/kg; i.p.). The rats were decapitated an hour later, the stomachs removed and the gastric mucosal damage scored. 1000 ng GLP-1 inhibited gastric mucosal damage by 45% and 10,000 ng GLP-1 by 60%. The specific receptor antagonist exendin-(9-39) (2500 ng/kg; i.p.), calcitonin gene related peptide (CGRP) receptor antagonist CGRP-(8-37) (10 microg/kg; i.p.), nitric oxide (NO) synthase inhibitor l-NAME (30 mg/kg; s.c.) and cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.) inhibited the preventive effect of GLP-1 on ethanol-induced gastric mucosal damage. GLP-1 also prevented the decrease in gastric mucosal blood flow caused by ethanol when administered at gastroprotective doses (1000 and 10,000 ng/kg; i.p.). In conclusion, GLP-1 administered peripherally prevents the gastric mucosal damage caused by ethanol in rats. CGRP, NO, prostaglandin and gastric mucosal blood flow are thought to play a role in this effect, mediated through receptors specific to GLP-1.
Isbil-Buyukcoskun
Naciye
N
Uludag University Medical Faculty, Department of Physiology, 16059, Gorukle, Bursa, Turkey. nisbil@uludag.edu.tr
Gulec
Guldal
G
Cam-Etoz
Betul
B
Ozluk
Kasim
K
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow
D010446:Peptide Fragments; D011453:Prostaglandins; D009569:Nitric Oxide; D000431:Ethanol; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin